The objectives of this study are to examine changes in genetic control of subspecies of cytochrome P-450 in the rat after treatment with polychlorinated biphenyls (PCBs), 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) and other environmental chemicals and to assess the implications of these changes. Present work emphasizes effects of PCBs and TCDD on the two major TCDD inducible isozymes (P-448MC and P-448MCB). A. AAF Metabolism. The contribution these two isozymes (P-448-MC and P-448-HCB) to metabolism of AAF in control and 3-MC induced microsomes was assessed. P-448-MC contributed chiefly to detoxification (ring hydroxylation) and P-448-HCB to N-hydroxylation (activation) in 3-MC induced microsome. B. Induction by a PCB Isomer: Dose response curves and time courses indicate that P-448-MC and P-448-HCB are coordinately induced by 3,4,5, 3',4',5'-HCB. Induction of mRNA was demonstrated in a cell-free system but the magnitude of induction of the mRNA did not totally account for the increase in protein. Antibodies are being raised to additional forms of rat liver P450 to be used as probes for quantitating changes due to environmental chemicals. We will attempt to clone DNA complementary to some of the rat P450s to use to analyze gene structure and changes in protein and mRNA synthesis after exposure to various chemicals. The goal of this project is to better understand the changes occurring after exposure to environmental chemicals. Antibodies and clones developed to these cytochromes will be useful in studying these effects.